Transferrin, the iron-binding protein of blood plasma, is the source of iron for the biosynthesis of hemoglobin by the reticulocyte. During its interaction with the reticulocyte, transferrin first combines with specific receptors on the reticulocyte membrane which are not present on mature cells. Our proposed research is concerned with the isolation and characterization of these receptors in an attempt to define the chemical basis by which they bind transferrin, thus making it possible for the protein to donate its iron to the cell. Since the binding of iron by the protein is strong enough to resist hydrolysis, and yet transferrin is conserved during its interaction with reticulocytes and other iron-requiring cells, specific mechanisms must exist for removal of iron from the protein by cellular structures. We are also concerned, therefore, with the chemical mechanisms involved in the physiologic disruption of the iron-protein bond. Another aspect of the proposed research deals with the structure of the two metal-binding sites of transferrin. Cr(III) is well known for the kinetic stability of its complexes. Transferrin with Cr(III) occupying its specific sites has been prepared and enzymatically degraded at physiologic pH. Peptides bearing Cr(III) will be isolated, acid-hydrolyzed, and subjected to amino acid analysis. This may provide new information about the amino acids which serve as ligands for specifically-bound metal ions in transferrin.